Primary pulmonary

Prostacyclin (epoprostanol) is one of the few drugs effective for the treatment of Primary Pulmonary Hypertension (PPH) a rare but frequently fatal illness of young adults. Increased blood pressure in the pulmonary circulation leads to right-heart failure. Continuous infusion of epoprostanol leads to a decrease in blood pressure however, it is unclear whether this is due to direct dilator activity of the IP receptor acting on smooth muscle, or a more indirect mechanism. 

Primary pulmonary hypertension is a disease of unclear etiology that is characterized by abnormally high mean pulmonary arterial pressures, in the absence of a demonstrable cause. A wide variety of pulmonary and cardiac diseases can lead to secondary pulmonary hypertension. 

Until recently, d-fenfiuramine was used to control appetite, in preference to d-amphetamine, because it has a lower affinity for the catecholamine transporter and so its uptake into noradrenergic and dopaminergic neurons is much less than that of amphetamine. This is thought to explain why, at anorectic doses, this compound lacks the psychotropic effects and dependence-liability that are real problems with if-amphetamine. Unfortunately, despite this therapeutic advantage, this compound has had to be withdrawn from the clinic because of worries that it might cause primary pulmonary hypertension, valvular heart disease and even long-term neuropathy. 

Spirometry, an objective measure of pulmonary function, can be used to assist in confirming the diagnosis of asthma. The primary pulmonary function tests used to assist in the diagnosis of asthma are the forced expiratory volume in... 

ET measured in the plasma appears to be a spillover of the ET that is (locally) released by the endothelium. It is known that low levels of ET (ranging from 0.25 to 5.0 pg/ml) are normally present in the circulation (B8, P12). These levels are increased by 3-10 times in patients with renal failure (S30), diabetes (V3), hypertension, bums (H32), myocardial infarction, primary pulmonary hypertension (N8), and cardiogenic shock (LI, L9, L10, PI, W8). ET is assumed to be released... 

After many health problems and deaths, the FDA removed Pondimin and Redux from market. Since then, there have been 200 reported cases of primary pulmonary hypertension relating to fen-phen and dexfen-phen. Of those cases, 40 have resulted in death. The FDA has received more than 100 reports of heart valve damage directly related to fen-phen or fenfluramine therapy there are no reports from individuals taking phentermine alone for weight loss. 

Therapy of coccidioidomycosis is difficult, and the results are unpredictable. Only 5% of infected persons require therapy. Candidates for therapy include those with severe primary pulmonary infection or concurrent risk factors (e.g., human immunodeficiency virus infection, organ transplant, or high doses of glucocorticoids), particularly patients with high complement fixation antibody titers in whom dissemination is likely. 

Blanpain, C., Le Poul, E., Parma, J., Knoop, C., Detheux, M., Parmentier, M., Vassart, G. and Abramowicz, M.J. (2003) Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension. Cardiovascular Research, 60 (3), 518-528. 

For instance, in September 2004, Bayer settled 2861 product liability cases for 1.09 billion for its cholesterol medicine cerivastatin (Baycol), which was linked to 100 deaths and withdrawn from market in 2001. In July 2004, the company settled 2771 cases for 1.06 billion. Bayer still has 7577 additional cases to settle (see Section 28.4.4.5 for additional information). In another example, a 1 billion jury verdict was upheld against Wyeth for its fenfluramine or dexfenfluramine and phentermine (Fen-Phen) drug combination, which was linked to primary pulmonary hypertension (PPH). Wyeth has set aside 16.6 billion to cover future liability on the drug (see Section 28.4.4.2 for more on this case). ... 

It is important to resolve whether primary structural damage in the liver causes subsequent lung and circulatory effects or whether primary pulmonary blockage is the cause of the circulatory effects and liver damage. 

Long-term treatment of New York Heart Association Class III and IV primary pulmonary hypertension IV Infusion Procedure to determine dose range Initially, 2 ng/kg/min, increased in increments of 2 ng/kg/min q 15min until dose-limiting adverse effects occur. Chronic Infusion Start at 4 ng/kg/min less than the maximum dose rate tolerated during acute dose ranging (or one half of the maximum rate if rate was less than 5 ng/kg/min). 

Unlabeled Uses Treatment of CHF, hypertension secondary to eclampsia and pre-eclampsia, primary pulmonary hypertension. 

Multivalvular heart disease, primary pulmonary hypertension and arrhythmias occur rarely... 

Primary pulmonary hypertension (PPH), psychotic episodes, and valvular heart disease rarely occur. 

Primary pulmonary hypertension and cardiac valve disorders have been associated with other centrally acting weight loss agents that cause release of serotonin from nerve terminals although sibutramine has not been associated with these effects in premarketing clinical studies, patients should be informed of the potential for these side effects and monitored closely for their occurrence... 

Initial studies of continuous intravenous prostacyclin infusion in patients with primary pulmonary hypertension have shown sustained improvement in pulmonary artery pressure, exercise capacity, and survival compared with... 

Intravenous epoprostenol increases exercise tolerance, improves pulmonary hemodynamics, and improves survival in patients with primary pulmonary hypertension. However, there are limitations to intravenous administration, and a significant proportion of patients develop catheter-related problems, such as thrombosis, pump failure, and catheter-related sepsis. In an attempt to improve delivery, several trials of aerosolized prostacyclin have been undertaken, primarily in patients with primary pulmonary hypertension. 

There has been a sequential comparison of inhaled nitric oxide 40 ppm with aerosolized iloprost 14— 17 micrograms in 35 adults with primary pulmonary hypertension (125). Five of the patients had minor headache and facial flushing during inhalation of iloprost, but these symptoms were short-lived and abated a few minutes after the inhalation ended. One patient had mild jaw pain after aerosolized iloprost, but again this was shortlived. There was an unexpected increase in pulmonary artery pressure in 10 patients and vascular resistance in six patients who received nitric oxide. The authors were uncertain of the cause of this increase, as nitric oxide generally behaves as a vasodilator, but they noted that... 

Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994 121(6) 409-15. 

Hoeper MM, Schwarze M, Ehlerding S, Adler-Schuermeyer A, Spiekerkoetter E, Niedermeyer J, Hamm M, Fabel H. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000 342(25) 1866-70. 

Interstitial pneumonia has been reported in a patient taking epoprostenol for primary pulmonary hypertension (6). 

Anticoagulants and continuous intravenous infusion of epoprostenol are the standard treatments for primary pulmonary hypertension. However, their combined use increases the likelihood of hemorrhagic complications, as demonstrated in a retrospective study of 31 consecutive patients with primary pulmonary hypertension (mean age, 29 years, 10 men, 21 women), nine of whom had 11 bleeding episodes nine episodes were cases of alveolar hemorrhage and two patients had severe respiratory distress (9). The mean dose of epoprostenol at the time of the first bleeding episode was 89 ng/kg/minute. More of the patients who had a bleeding episode died (67% versus 41%). 

McLaughlin VV, Genthner DE, Panella MM, Rich S. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998 338(5) 273-7. 

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